Intratumoral CD8(+) T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancer
- Author(s)
- Virassamy, B; Caramia, F; Savas, P; Sant, S; Wang, J; Christo, SN; Byrne, A; Clarke, K; Brown, E; Teo, ZL; von Scheidt, B; Freestone, D; Gandolfo, LC; Weber, K; Teply-Szymanski, J; Li, R; Luen, SJ; Denkert, C; Loibl, S; Lucas, O; Swanton, C; Speed, TP; Darcy, PK; Neeson, PJ; Mackay, LK; Loi, S;
- Journal Title
- Cell Reports
- Publication Type
- epub ahead of print
- Abstract
- CD8(+) tumor-infiltrating lymphocytes with a tissue-resident memory T (T(RM)) cell phenotype are associated with favorable prognosis in patients with triple-negative breast cancer (TNBC). However, the relative contribution of CD8(+) T(RM) cells to anti-tumor immunity and immune checkpoint blockade efficacy in breast cancer remains unknown. Here, we show that intratumoral CD8(+) T cells in murine mammary tumors transcriptionally resemble those from TNBC patients. Phenotypic and transcriptional studies established two intratumoral sub-populations: one more enriched in markers of terminal exhaustion (T(EX)-like) and the other with a bona fide resident phenotype (T(RM)-like). Treatment with anti-PD-1 and anti-CTLA-4 therapy resulted in expansion of these intratumoral populations, with the T(RM)-like subset displaying significantly enhanced cytotoxic capacity. T(RM)-like CD8(+) T cells could also provide local immune protection against tumor rechallenge and a T(RM) gene signature extracted from tumor-free tissue was significantly associated with improved clinical outcomes in TNBC patients treated with checkpoint inhibitors.
- Publisher
- Cell Press
- Keywords
- Ctla-4; Pd-1; cancer immune surveillance; cancer immunotherapy; immune checkpoint blockade; intratumoral CD8(+) T cells; tissue-resident memory cells; triple-negative breast cancer; tumor immunity; tumor infiltrating lymphocytes
- Research Division(s)
- Bioinformatics
- PubMed ID
- 36827978
- Publisher's Version
- https://doi.org/10.1016/j.ccell.2023.01.004
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-03-08 03:16:10
Last Modified: 2023-03-08 04:08:13